Mechanisms of allergy
Substance P and its receptor neurokinin 1 expression in asthmatic airways,☆☆

https://doi.org/10.1067/mai.2000.109829Get rights and content

Abstract

Background: Neural mechanisms have been suggested to contribute to the pathogenesis of chronic asthma. The expression of neuropeptides such as substance P may be regulated by infectious pathogens, including Mycoplasma species. In contrast to substance P, the substance P receptor neurokinin 1 has not been examined at the protein level in asthmatic airways. Objective: This study evaluated substance P and neurokinin 1 protein expression and mucus content in endobronchial biopsy specimens from normal control subjects and asthmatic subjects. Detection of Mycoplasma pneumoniae was performed in both biopsy and bronchoalveolar lavage specimens. Methods: Biopsy specimens were collected from 10 normal control subjects and 18 asthmatic subjects before and after a 6-week treatment with a macrolide antibiotic (n = 11) or placebo (n = 7) and were stained for substance P, neurokinin 1, and mucus. M pneumoniae was evaluated by PCR. Results: At baseline, compared with normal control subjects, asthmatic subjects demonstrated increased expression of substance P and neurokinin 1 and mucus content in the airway epithelium. Epithelial mucus content correlated with epithelial substance P expression (r s = 0.45, P = .04) and FEV1 percent predicted (r s = –0.51, P = .019). After antibiotic treatment, both epithelial substance P and neurokinin 1 expression were significantly reduced in asthmatic subjects. M pneumoniae was found in 8 of 18 asthmatic subjects. Asthmatic subjects with M pneumoniae , compared with those without M pneumoniae , showed higher baseline epithelial neurokinin 1 expression, which was significantly reduced after antibiotic treatment (P = .02). Conclusion: Our data suggest that abnormalities in neural mechanisms may exist in the epithelium of asthmatic airways, and M pneumoniae is possibly involved in this process. Antibiotic intervention may be effective in the treatment of asthma partly through the downregulation of the neurogenic process. (J Allergy Clin Immunol 2000;106:713-22.)

Section snippets

Subjects

Twenty-eight subjects were recruited by means of newspaper and radio advertisements from the general community of Denver, Colorado. Eleven of these subjects came from our previous report of M pneumoniae detection by means of PCR,15 and 17 subjects were new to this study. The asthmatic subjects fulfilled criteria for asthma exhibiting a PC20 to methacholine of less than 8 mg/mL and reversibility of lung function by at least 15% with a bronchodilator. Control subjects exhibited no evidence of

Subjects

The characteristics of asthmatic and normal control subjects are shown in Table I.

. Subject characteristics

Empty CellAsthmatic subjects (n = 18)Control subjects (n = 10)
Sex (M/F)10/86/4
Age (y)34.0 ± 2.230.7 ± 2.4
Duration of asthma (y)22.9 ± 2.8
FEV1 (L)2.4 ± 0.24.2 ± 0.3*
FEV1 (% predicted)65.6 ± 4.8103.8 ± 5.2*
PC20 (mg/mL)0.27 ± 0.06>18*
MedicationsICS (n = 5), β-agonist (n = 18)None
*P < .01 compared with asthmatic subjects.

ICS, Inhaled corticosteroids.

The sex distribution and the age of subjects were

Discussion

This study demonstrates that compared with normal control subjects, asthmatic subjects have increased expression of substance P and its receptor neurokinin 1 in the airway epithelium but not in the submucosa. Consistent with this finding, increased mucus production was also observed in asthmatic subjects, and it was inversely correlated with FEV1. The increased epithelial substance P and neurokinin 1 expression in asthmatic subjects appears to be associated with the detection of M pneumoniae in

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    Supported by the American Lung Association-ARC and the National Heart, Lung and Blood Institute (HL 36577).

    ☆☆

    Reprint requests: Richard J. Martin, MD, National Jewish Medical and Research Center, 1400 Jackson St, Room J116, Denver, CO 80206.

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